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Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability

Author

Listed:
  • Xiangxi Wang

    (Chinese Academy of Science)

  • Shi-Hua Li

    (Beijing Institute of Microbiology and Epidemiology)

  • Ling Zhu

    (University of Oxford)

  • Qing-Gong Nian

    (Beijing Institute of Microbiology and Epidemiology)

  • Shuai Yuan

    (Chinese Academy of Science)

  • Qiang Gao

    (Chinese Academy of Science
    Sinovac Biotech Co., Ltd.)

  • Zhongyu Hu

    (National Institutes for Food and Drug Control)

  • Qing Ye

    (Beijing Institute of Microbiology and Epidemiology)

  • Xiao-Feng Li

    (Beijing Institute of Microbiology and Epidemiology
    State Key Laboratory of Pathogen and Biosecurity)

  • Dong-Yang Xie

    (Beijing Institute of Microbiology and Epidemiology
    Anhui Medical University)

  • Neil Shaw

    (Chinese Academy of Science)

  • Junzhi Wang

    (National Institutes for Food and Drug Control)

  • Thomas S. Walter

    (University of Oxford)

  • Juha T. Huiskonen

    (University of Oxford)

  • Elizabeth E. Fry

    (University of Oxford)

  • Cheng-Feng Qin

    (Beijing Institute of Microbiology and Epidemiology
    State Key Laboratory of Pathogen and Biosecurity
    Anhui Medical University)

  • David I. Stuart

    (University of Oxford
    Harwell Science and Innovation Campus)

  • Zihe Rao

    (Chinese Academy of Science
    Tsinghua University)

Abstract

Although several different flaviviruses may cause encephalitis, Japanese encephalitis virus is the most significant, being responsible for thousands of deaths each year in Asia. The structural and molecular basis of this encephalitis is not fully understood. Here, we report the cryo-electron microscopy structure of mature Japanese encephalitis virus at near-atomic resolution, which reveals an unusual “hole” on the surface, surrounded by five encephalitic-specific motifs implicated in receptor binding. Glu138 of E, which is highly conserved in encephalitic flaviviruses, maps onto one of these motifs and is essential for binding to neuroblastoma cells, with the E138K mutation abrogating the neurovirulence and neuroinvasiveness of Japanese encephalitis virus in mice. We also identify structural elements modulating viral stability, notably Gln264 of E, which, when replaced by His264 strengthens a hydrogen-bonding network, leading to a more stable virus. These studies unveil determinants of neurovirulence and stability in Japanese encephalitis virus, opening up new avenues for therapeutic interventions against neurotropic flaviviruses.

Suggested Citation

  • Xiangxi Wang & Shi-Hua Li & Ling Zhu & Qing-Gong Nian & Shuai Yuan & Qiang Gao & Zhongyu Hu & Qing Ye & Xiao-Feng Li & Dong-Yang Xie & Neil Shaw & Junzhi Wang & Thomas S. Walter & Juha T. Huiskonen & , 2017. "Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00024-6
    DOI: 10.1038/s41467-017-00024-6
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